Is PRMT3 p.Pro416Arg (c.1247C>G) pathogenic?

PRMT3 p.Pro416Arg (c.1247C>G) is classified Uncertain significance in PRMT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-24). AlphaMissense: likely benign (0.2157); Ultra-rare (popmax 0.0155%, nfe).

How common is PRMT3 p.Pro416Arg (c.1247C>G) in the general population?

PRMT3 p.Pro416Arg (c.1247C>G) is ultra-rare (popmax 0.0155%, nfe) (gnomAD).

What do computational predictors say about PRMT3 p.Pro416Arg (c.1247C>G)?

AlphaMissense predicts likely benign (score 0.2157) — an in-silico prediction, not a clinical call.

PRMT3 p.Pro416Arg

c.1247C>G · VCV3938303

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2157 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0155%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2157	likely benign
REVEL	0.384	indeterminate
SaProt	LLR -11.11	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 0.99
Regional constraint	o/e 1.03	unconstrained · MANE · 121 kb · p 0.43 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0155% European (non-Finnish) · 182/1,173,780 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.016% 256/1,604,766 alleles · ultra-rare exomes 227/1,452,632 · genomes 29/152,134 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.102%	980
European (non-Finnish)grpmax	0.0155%	6,449
Remaining individualsnot grpmax-eligible	0.0113%	8,861
African / African-American	0.00267%	37,388

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PRMT3
Protein: p.Pro416Arg
Coding: c.1247C>G
MANE Select: NM_005788
Type: single nucleotide variant
Location: chr11:20462154 (GRCh38)
Gene constraint: LOEUF 1.167 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.63 · 10 PDB
Residue 416: the sam-dependent mtase prmt-type domain; the 'mediates interaction with aldh1a1' region

Full PRMT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRMT3 p.Ala210Val Benign ★★ same type
PRMT3 p.Ala175Thr Uncertain significance ★ ⚠ same type
PRMT3 p.Ala210Glu Uncertain significance ★ ⚠ same type
PRMT3 p.Ala276Pro Uncertain significance ★ ⚠ same type
PRMT3 p.Ala31Thr Uncertain significance ★ ⚠ same type
PRMT3 p.Arg12Gln Uncertain significance ★ ⚠ same type
PRMT3 p.Arg180Cys Uncertain significance ★ ⚠ same type
PRMT3 p.Arg180His Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/prmt3-p-pro416arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown